Synthetic veins for heart bypass

Scientists have grown human veins in a laboratory, in a breakthrough that could revolutionise heart bypass surgery, reported the Daily Mail.

The news comes from research in which scientists developed a method for using human muscle tissue to create human blood vessels in the laboratory. These were then tested in animals, where they showed “excellent” blood flow and resistance to blockages and other complications. The vessels could also be safely refrigerated for up to a year.

This initial animal research has suggested that it may be possible in the future to use these synthesized vessels in humans, for example in coronary artery bypass operations, which currently rely on patients providing a healthy blood vessel to form their bypass graft. However, this short, preliminary research was in its early stages and therefore scientists will need to undertake many further stages of research before these lab-grown veins are proven to be safe and effective in humans.

Where did the story come from?

The study was carried out by researchers from East Carolina University, Duke University, Yale University and Humacyte Inc, a company involved in commercially developing products for vascular disease. The research was also funded by Humacyte and the study was published in the peer-reviewed journal, Science Translational Medicine.

The newspapers reported the research accurately, although they tended to reflect the optimism of the scientists rather than the limitations of the research. The Daily Telegraph’s report that the new veins can be “safely transplanted into any patient” is not supported by the research conducted so far. The BBC’s report quoted independent experts who correctly pointed out that this is early research, and the Daily Mail also highlighted that the veins were unlikely to be available to patients for several years.

What kind of research was this?

This was laboratory research in which scientists engineered vascular grafts (called Tissue Engineered Vascular Grafts, or TEVGs) from human and dog muscle and tested them in baboon and dog models.

The researchers point out that there is considerable need for readily available vascular grafts in areas such as coronary artery bypass and peripheral vascular surgery, and also for providing arteriovenous (AV) access in patients with kidney failure who need haemodialysis. When treating coronary artery disease and peripheral arterial disease, surgeons often create a graft using blood vessels taken from another part of the body, but in many cases this is not suitable, for example if the desired blood vessel is diseased.

Patients who need haemodialysis are often given grafts made from materials like plastic, but this can also be problematic. Other attempts have been made to develop TEVGs and some have been trialled in patients.

However, the researchers say these have had problems that make them impractical for use, such as high production costs and a lengthy production process.

What did the research involve?

In this year-long study scientists used human and canine smooth muscle cells, which they cultured into tubes using a synthetic “scaffold”. This scaffold dissolved and the cellular material was killed off with detergent to ensure the remaining material could be implanted without causing an immune reaction. The bioengineered veins (TEVGs) were stored for 12 months at a temperature of 4C.

Scientists then tested the feasibility of the TEVGs on nine adult male baboons and five mongrel dogs. They operated on the baboons, using the TEVGs to provide arteriovenous grafts, which is where an artificial blood vessel is used to join an artery and vein, usually for the purpose of haemodialysis. They also performed surgery on the dogs to see how well the bioengineered tissue functioned as a coronary artery bypass graft (CABG), where the artificial vessels were grafted to the coronary arteries, and as a peripheral artery bypass, where a graft is used to reroute a blocked artery in the leg.

They used specialised techniques to assess the animals’ immune response and ultrasound and medical imaging techniques to monitor the grafts. The animals were anaesthetised for access.

What were the basic results?

After one year of storage, the researchers found that the TEVGs showed the same properties as natural human blood vessels. The baboon and dog studies showed that the TEVGs:

• had “excellent patency” (blood flow)
• integrated well with existing blood vessels
• resisted dilatation, which means they did not expand
• resisted calcification, which means they did not harden through a build-up of calcium salts
• resisted intimal hyperplasia (thickening)

The researchers say that the latter three findings suggest that the TEGVs do not provoke an immune response that could lead to problems with the graft.

How did the researchers interpret the results?

The researchers say that tissue-engineered vascular grafts could provide a readily available option for patients needing bypasses and graft surgery but who cannot provide their own tissue or who are not candidates for inorganic grafts.

They also say that using human cells to produce TEVGs (which are chemically stripped of their genetic material) would allow one human donor to provide grafts for dozens of patients. Pooling cells from multiple donors would allow for the establishment of large cell banks, for engineering TEVGs.

Conclusion

This research is interesting and could lead to some promising developments in procedures where grafts are needed for surgery, such as coronary artery bypass. However, as the researchers point out it has its limitations:

• In the baboon model, the frequency with which they could monitor the graft was restricted due to having to anaesthetise the animals each time they were examined.
• In the canine model, only a small number of TEVGs were evaluated for coronary bypass and additional studies are needed to evaluate their feasibility, in particular if they have the strength to withstand “the force of cardiac motion”.

In conclusion, although this study is of interest, the research is still at an early stage. It has demonstrated a method for producing potentially suitable grafts, but has not established their safety or practicality in human patients. Far more evidence needs to be gathered about the long-term safety and effectiveness of TEVG before they could be used in patients.